System and method for detecting, localizing, and characterizing occlusions, stent positioning, dissections and aneurysms in a vessel

ABSTRACT

This invention relates to a method and devices for detection, localization and characterization of occlusions, aneurysms, dissections stent position, dissections stent mal-position, wall characteristics and vascular bed. The invention is based on introducing an artificial pressure or flow excitation signal (a single signal or more) into the blood vessel (or in other tubular flowing fluid conduits), measurement and analysis of the pressure and or flow. The invention discloses a method and devices for detection and characterization of partial or total occlusion or aneurysm in blood vessels or in other tubular flowing fluid conduits within a body, such as urine flow in the urethra.

FIELD OF THE INVENTION

This invention relates to the field of medical interventional diagnosticdevices. In particular, this invention provides a system and method forthe detection, localization, and characterization of occlusions andaneurysms in blood or other body vessels and to the evaluation ofclinical treatment success (e.g. tracking sufficient opening of theocclusion or malpositioning of a stent). Also, this invention provides amethod and system for vessel wall characterization and diagnosis of thevascular bed.

BACKGROUND OF THE INVENTION

Vascular diseases are often manifested by reduced blood flow due toatherosclerotic occlusion of vessels. For example, occlusion of thecoronary arteries supplying blood to the heart muscle is a major causeof heart disease. Invasive procedures for relieving arterial blockagesuch as bypass surgery and balloon dilatation with a catheter arecurrently performed relying on estimates of the occlusioncharacteristics and the blood flow through the occluded artery. Theseestimates are based on measurements of occlusion size and/or blood flowor blood pressure before and after the stenosis. Unfortunately, currentmethods of occlusion size and blood flow measurement have lowresolution, are inaccurate, are time consuming, require expertise in theinterpretation of the results and are expensive. Thus, decisions onwhether or not to use any of the blockage relieving methods and which ofthe methods should be used are often based on partial information. Theevaluation of therapeutic success is also problematic, where bothocclusion opening and stent position must be evaluated.

Typically, the physician first selects the appropriate treatment methodfrom among medication therapy, transcatheter cardiovascular therapeutics(TCT), coronary artery bypass grafting (CABG), or non-treatment.Atherosclerotic lesions may have different characteristics. Some lesionsexhibit a variable degree of calcification while others have a fatty orthrombotic nature. Lesion characteristics together with vessel conditiondistal to the lesion and the vascular bed (VB) condition are the majorfactors for determining the therapeutic procedure needed. Recently,increasing numbers of patients are directed toward TCT. TCT starts withan interventional diagnosis procedure (most commonly used inangiography), followed by the treatment of the patient with medicationtherapy, CABG or continuation of the TCT procedure with adequateinterventional treatment. TCT final stage include diagnosis tools, forthe evaluation of treatment success.

Numerous methods are currently available for treating various lesiontypes. Some of these methods are given herein below, sequenced from“softer” to “heavier”, relating to their ability to open calcifiedlesions; percutaneous transluminal angioplasty (PTCA), “Cutting balloon”angioplasty, directional coronary atherectomy (DCA), rotational coronaryatherectomy (RCA), Ultrasonic breaking catheter angioplasty,transluminal extraction catheter (TEC) atherectomy, Rotablatoratherectomy, and excimer laser angioplasty (ELCA). Often, stents areplaced within the lesion so as to prevent re-closure of the vessel (alsoknown as recoil). If the stent is malpositioned, it disrupts the flowand may initiate restenosis.

Lesion characteristics, together with vessel condition proximal anddistal to the lesion and vascular bed condition are used to determinethe medically and economically optimal treatment method or combinationof methods of choice. The main geometrical parameter of the lesion isstenosis severity As/Ao. Here As is the minimal open cross-sectionalarea of the stenosis and Ao is the nominal cross-sectional area of theunobstructed vessel. The second parameter is the stenosis length.Another clinically important lesion characteristic is the lesioncalcification level. A non-calcified arterial wall or lesion is usuallya non-chronic, fat based plaque that may be treated by medicationtherapy, or by the softer, less expensive, PTCA method. Heavilycalcified lesion typically requires harder methods, such as ELCA. Thecalcification level influences the decision whether to use a dilatationballoon prior to stenting. For example, in cases of very soft lesions,the physician may elect not to use a dilatation balloon prior tostenting. In cases where the degree of calcification dictate the use ofsuch a balloon, the vessel wall calcification level influences theoptimal inflation pressure of the dilatation balloon. Chapter 12entitled “CALCIFIED LESIONS” of the book “The New Manual ofInterventional Cardiology” (Eds. Mark Freed, Cindy Grines and Robert D.Safian, Physicians' Press, Birmingham, Mich., 1996, pp. 251-261),discusses various methods for the assessment of the degree of vesselwall calcification and their importance in selecting a treatment method.

Decisions about post dilatation processes such as stent deployment forpreventing wall recoil and restenosis, or radiation exposure forpreventing restenosis caused by cell proliferation, are also influencedby vessel wall and lesion characteristics. Unfortunately, while lesiongeometry is evaluated by angiography, qualitative coronary angiography(QCA), or by intravascular ultrasound (IVUS), accurate informationregarding the vessel wall structure and composition and the degree ofcalcification of the lesion and of the vessel wall sections neighboringthe lesion is frequently unavailable due to the expenses involved inobtaining this information. Angiography has been the main diagnostictool in the cath lab. The physician interprets angiographical images inthe following sequence: identification and location of the severelesions, evaluation of the occlusion level (in diameter percentage ofthe occluded portion), qualitative estimation of the perfusion accordingto “thrombolysis in myocardial infarction” (TIMI) grades, determinedaccording to the contrast material appearance. TIMI grades 0, 1, 2, 3represent no perfusion, minimal perfusion, partial perfusion andcomplete perfusion, respectively.

Among the more sophisticated diagnostic tools are qualitative coronaryangiography (QCA), intravascular ultrasound (IVUS), intravascularDoppler velocity sensor (IDVS) and intravascular pressure sensor (IPS).QCA calculates geometrical properties from angiographic images, in imagezones that are chosen by the physician. IVUS provides accurategeometrical data regarding cross section and accurate informationregarding the vessel wall structure and composition. Physiologicalparameters have been introduced in order to help the clinician to electthe appropriate clinical solution. IDVS provides velocity measurements,enabling discriminating various degrees of occlusion according tocoronary flow reserve (CFR) criteria. IDVS suffers from inaccuracyproblems resulting from positioning error within the vessel.

IPS provides pressure measurements enabling discriminating variousdegrees of occlusion according to the FFR (fractional flow reserve)criteria and according to the pressure drop across the stenosis. Whilemeasuring the pressure based parameters, the transducer should cross thestenosis and measure pressure downstream of the stenosis. The need tocross the stenosis prevents the use of this parameters for purelydiagnostic purposes, since stenosis crossing is considered of high riskand therefore, unjustified for diagnostic purposes.

Angiography and the sophisticated techniques discussed above may beemployed prior to and after therapeutic procedure (the last for theevaluation of the results and decision about correcting actions).unfortunately, the above discussed sophisticated methods are rarely useddue to their high price, operation complexity and the prevailing feelingamong physicians that while they provide more accurate information, thisinformation usually does not contribute to clinical decisions.

Pressure, flow and geometry are three variables often measured in thecardiovascular system. Recent progress in invasive probeminiaturization, improvements of the frequency response of probe sensorsand computerized processing have opened a whole new range ofintravascular pressure and flow measurements and analysis that have beenpreviously impossible to perform. A method for determination of thereflection sites in the arterial system was suggested by Pythoud, F.Stergiopulos, N. Westerhof, N. and Meister, J. J. in “Method fordetermining distributions of reflection sites in the arterial system” inAm. J. Physiol 271 (1996). They studied reflections of pressure and flowwaves generated by the beating heart, in the arterial tree usingsimultaneous pressure and flow measurements. The low (up to 10 Hz)bandwidth of the pressure and flow signals prevent accuratedetermination of the distance to reflection site by these authors.Correct determination of reflection source location requires accurateestimation of the pressure wave velocity (PWV) in the vessels underconsideration and under the specific pressure signal, in contrast withliterature data that is based on healthy arteries under beating heartpulses. All known methods for PWV measurement, used two, three or moresimultaneous measurements, which prove impractical consideringclinically available tools and methods. Further, various attempts havebeen done to analyze pressure and flow wave changes caused by occludedsites. Harmonic distortions, changes in pressure wave velocity phasevelocity, wave attenuation, and additional reflection sites within thearterial tree prevent successful interpretation and implementationwithin clinical methods or tools.

SUMMARY OF THE INVENTION

The invention discloses a method and devices for detection, localizationand characterization of occlusions, aneurysms, wall characteristics andvascular bed by introducing an artificial pressure or flow excitationsignal (a single signal or multiple signals) into the blood vessel (orin any other tubular flowing fluid conduits), measurement and analysisof the pressure and or flow. The invention provides a method and devicesfor detection and characterization of partial or total occlusion oraneurysm in blood vessels or in other tubular flowing fluid conduitswithin a body, such as urine flow in the urethra.

This invention provides a method and devices may also serve forevaluating the success of medical treatment. For example trackingsufficient opening of the occlusion or malpositioning of a stent. It mayalso serve for the characterization of vascular bed, downstream thevessel.

The present invention includes also a method for further analysis of theresponse to the excitation signal yielding a quantitative determinationof elastic properties of blood vessel walls for characterizing, interalia, the distensibility and the compliance of lesioned and non-lesionedparts of blood vessels. The derived elastic properties may be furtherused to determine the degree of calcification of lesioned andnon-lesioned parts of blood vessels.

This invention provides an apparatus for detecting, locating andcharacterizing changes in a tubular conduit system within a living bodyfor transferring fluids, said apparatus comprising: a signal generatorconfigured to transmit into said tubular conduit a probe signal thatchanges in response to encountering changes in said tubular conduitsystem; a signal sensor operative to receive said probe signal followingtransmission into said tubular conduit system; a processor unitoperatively connected to said signal sensor; a program for controllingthe processor unit; said processor unit operative with said program toreceive said probe signal following transmission through said tubularconduit system: identify changes in said probe signal; detectcharacteristics of said tubular conduit system, said characteristics ofsaid tubular conduit system being derived from changes in said probesignal; and recognize and assign a label said characteristic of saidtubular conduit said system.

This invention provides a processor apparatus for detecting, locatingand characterizing changes in a tubular conduit system within a livingbody for transferring fluids for use with a signal generator configuredto transmit into said tubular conduit a probe signal that changes inresponse to encountering changes in said tubular conduit system and asignal sensor operative to receive said probe signal followingtransmission into said tubular conduit system, said processor apparatuscomprising: a processor unit operatively connected to said signalsensor; a program for controlling the processor unit; said processorunit operative with said program to receive said probe signal followingtransmission through said tubular conduit system: identify changes insaid probe signal; detect characteristics of said tubular conduitsystem, said characteristics of said tubular conduit system beingderived from changes in said probe signal; recognize and assign a labelsaid characteristic of said tubular conduit said system; and ascertainand assign a value corresponding to the location and size of saidcharacteristic of said tubular conduit.

This invention provides a method for using a computer to detect, locateand characterize changes in a tubular conduit system within a livingbody for transferring fluids wherein said computer is operativelyconnected to a signal generator configured to transmit into said tubularconduit a probe signal that changes in response to encountering changesin said tubular conduit system and a signal sensor operative to receivesaid probe signal following transmission into said tubular conduitsystem, said method comprising the steps of: receiving said probe signalfollowing transmission through said tubular conduit system: identifychanges in said probe signal; detecting characteristics of said tubularconduit system, said characteristics of said tubular conduit systembeing derived from changes in said probe signal; and recognizing andassigning a label said characteristic of said tubular conduit saidsystem.

Lastly, the present invention includes also a method for furtheranalysis of the response to the excitation signal yielding aquantitative determination of elastic properties of blood vessel wallsfor characterizing, inter alia, the distensibility and the compliance oflesioned and non-lesioned parts of blood vessels. The derived elasticproperties may be further used to determine the degree of calcificationof lesioned and non-lesioned parts of blood vessels.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be understood and appreciated more fully fromthe following detailed description taken in conjunction with theappended drawings in which like components are designated by likereference numerals:

FIG. 1 is a schematic view of a clinical system used for characterizinglesions, aneurysm or vascular bed in blood vessels, constructed andoperative in accordance with a preferred embodiment of this invention.

FIG. 2 is a schematic functional block diagram illustrating the detailsof clinical system 1 of FIG. 1.

FIG. 3 is schematic cross section illustrating the positioning of thesensors, the pressure signal generator (PSG) and the catheter of thesystem 1 of FIG. 1 within an obstructed blood vessel during theoperation of the system.

FIG. 4 is a schematic cross section illustrating one embodiment of thePSG unit 5 of FIG. 1 which was used in preliminary in-vivo studies.

FIG. 5 is a schematic view of an in-vitro system used for characterizinglesions, aneurysm or vascular bed in blood vessels.

FIG. 6 is schematic cross section illustrating the in-vitrorecirculating system 51 of system 41 of FIG. 5.

FIG. 7 is schematic cross section illustrating the positioning of thesensors, the pressure signal generator (PSG) and the catheter of thesystem 51 of FIG. 6 during the operation of the system.

FIG. 8 is a schematic cross section illustrating one embodiment of thePSG unit 5 of FIG. 5 which was used in preliminary in-vitro studies.

FIG. 9 is isometric description of the setup used in Method 1 includingthe PSG unit, the signal pressure sensor and the catheter within a bloodvessel.

FIG. 10 is isometric description of a pig carotid exposed and partiallyoccluded in an in-vivo study, including the PSG unit and the singlepressure sensor.

FIG. 11 is an isometric description of the setup used in Method 5including the PSG unit, the two pressure sensors and the catheter withina blood vessel without stenosis.

FIG. 12 is a graph describing pressure versus time (no. of samples) in atwo pressure sensors measurement in-vitro setup as shown in FIG. 11.

FIG. 13 is an isometric description of the setup used in Method 5including the PSG unit, the two pressure sensors and the catheter withina stenosed blood vessel.

FIG. 14 is a graph describing pressure versus time (no. of samples) in atwo pressure sensors measurement in-vitro setup as shown in FIG. 13.

FIG. 15 is a graph describing the pressure time derivative versus time(number of samples) as calculated from the data described in FIG. 12.

FIG. 16 is a graph describing the pressure time derivative versus time(number of samples) as calculated from the data described in FIG. 14.

FIG. 17 is a demonstration of the calculation of the stenosis severityas the area ratio of the two peaks resulting from Procedure 1.

FIG. 18 is an isometric description of the setup used in Method 4including the PSG unit, a pressure sensor measuring at two points A andB, and a catheter within a stenosed blood vessel.

FIGS. 19(a)-19(e) present the result of the analysis which separate theforward and backward signals.

FIG. 20 is schematic cross section illustrating the in-vitrorecirculating system 51 of system 41 of FIG. 5, with the addition of anultrasonic flowmeter 65 and a stenosis 55.

FIG. 21 is a graph describing the flow (ml/min) versus time (no. ofsamples) measured within the in-vitro system 51 of FIG. 6, and with astenosis at a distance of 95 cm.

FIG. 22 is a graph describing the flow (ml/min) versus time (no. ofsamples) measured within the in-vitro system 51 of FIG. 6, and with astenosis at a distance of 50 cm.

FIG. 23 is a graph of two pressure measurements, demonstrating thecalculation of pressure wave velocity using Procedure 3.

FIG. 24 is a graph of two pressure measurements, using the in-vitrosystem of FIGS. 5-7 and a Bio-Tek pressure calibrator as a pressuregenerator PSG demonstrating the forward and reflected signals.

FIG. 25 is a graph describing the pressure as measured in an in-vivostudy, in an occluded vessel, after application of an excitationpressure, in a system as described in FIG. 10.

FIG. 26 is a closed view of the signal presented in FIG. 25.

FIG. 27 is the result of Procedure 2 applied to the data presented inFIGS. 25 and 26, illustrating the separation into two peaks, for theforward and backward signals.

FIG. 28 is the result of Procedure 1 applied in a long range case aspresented in Method no. 2. The upper signal is the analysis result ofthe measured signal presented in the lower figure.

FIGS. 29(a)-29(B). FIG. 29(a) is a schematic of an impulse generator.The generator could generate pulses with different width from 2 microsec. To 1.6 sec. And with period (distance between pulses) from 2 microsec. To 2.3 sec. For better adjustment the width and the period aredivided to 6 regions and related by 4 separate regulators, 2 for periodand 3 for the pulse width. The electric pulse generator work from powersupply of 9 V. The standard timer microchip 556. FIG. 29(b) is aschematic showing electric pulse generator connected to externalequipment which will transfer the electric impulse to an impulse offlow/pressure.

FIG. 30 schematic showing use of a Bioteck apparatus.

FIG. 31 is a block diagram of a PSG device having a pump with anelectromagnetic push/pull mechanism.

FIG. 32 is a block diagram of a PSG device having an externalelectromagnetic hammer operative to punch a full-of-fluid membrane.

FIG. 33 is a block diagram of a PSG device having two separate membranevolumes, one with high pressure in which an external electromagnetichammer moves or destroys a membrane separating the chambers.

FIG. 34 is a block diagram of a PSG device having a two way linearlyProportional Flow Control Valve operated by straight DC drive signals.

DETAILED DESCRIPTION OF THE INVENTION

the form of the pressure and flow wave changes at different locationsalong the arterial system. The most obvious reason is reflection of theadvancing pulse originating by the heart beat from occlusions. Analysisof the pressure and or flow waveform as demonstrated herein identifiesand quantifies abnormalities within arteries, mainly occlusions.Pressure wave velocity has its own clinical value as a measure ofdistensibility or compliance. Significant changes are observed in thehemodynamic characteristics of blood vessels with aging and/ordisease-state such as hypertension and atherosclerosis. The nature ofheart beat rather than low bandwidth and its heart generated pulsevariance complicates PWV calculations. The variability of pulse sourcesbeating heart imposes inherent variance between measurements takeneither in different patients and even between measurements taken in thesame patient but at different times or even the same patient, same timedifferent artery. Basically, the large arteries dilate and stiffen, thecollagen/elastin ratio increases, thus reducing the vesseldistensibility. For example, the elastic modulus of the human aorta,more than doubles between the age of 20 and 60 years. The diameter ofthe human ascending aorta increases by 9% per decade, and the aorta wallthickens to a larger extent, raising the ratio of the vessel wallthickness to the vessel's radius. These processes result in an increasedpressure wave velocity (PWV) within the vessel. Calcification of thevessel wall in particular regions causes significant increase in PWV inthe calcified region.

Regions where PWV increases and decreases along the blood vessel asdemonstrated herein mark the calcified zone boundaries, and the increasein the PWV above a reference value are used for evaluating thecompliance and the calcification level. The determined value of the PWVare compared to the average PWV value, predetermined statistically forthe same blood vessel in a specific age and gender group to which thecurrent patient belongs by calculating and reporting their ratio.Additionally, the PWV value determined within the lesion region may becompared to the PWV value(s) determined within one or more non-lesionregions of the same vessel which serve as an internal reference value,by calculating and reporting the ratio of the above PWV values. ThesePWV measurements and the reported PWV ratio disclosed hereinabove, areuseful in the detection of otherwise “angiographically occult” diseasedvessel regions.

This invention provides an apparatus for detecting, locating andcharacterizing changes in a tubular conduit system within a living bodyfor transferring fluids, said apparatus comprising: a signal generatorconfigured to transmit into said tubular conduit a probe signal thatchanges in response to encountering changes in said tubular conduitsystem; a signal sensor operative to receive said probe signal followingtransmission into said tubular conduit system; a processor unitoperatively connected to said signal sensor; a program for controllingthe processor unit; said processor unit operative with said program toreceive said probe signal following transmission through said tubularconduit system: identify changes in said probe signal; detectcharacteristics of said tubular conduit system, said characteristics ofsaid tubular conduit system being derived from changes in said probesignal; and recognize and assign a label said characteristic of saidtubular conduit said system.

In one embodiment the pressure signal originates from catheterizationlaboratory injection system. The signal may be either one of theinternally generated waveforms or excited electronically from a separatesignal generator either a stand alone unit or integrated within thesystem computer, otherwise used for data acquisition and analysis. Inanother embodiment the pressure signal may originate from an impactmechanism system, e.g. a spring loaded or electronically activatedmechanical impact system, applying pressure on either the catheter or ona container attached to it. In one embodiment the processor unit isoperative to select a method from a plurality of methods to identifychanges in said probe signal and therefrom detect changes in saidtubular conduit system. For example, the processor unit is operative todetect aneurysms, stenosis, and/or arterial occlusions.

The method is based on introducing an artificial pressure signal intothe blood vessel. In one embodiment the pressure signal originates froma pressure signal generator (PSG). For example, a PSG of the typesuitable for this purpose is a “blood pressure systems calibrator” model601A, commercially available from Bio-Tek Instruments Inc., HighlandPark, Box 998, Winooski, Vt.-05404-0998, U.S.A. Catheterizationlaboratory injection systems are known to those skilled in the art. Forexample, a system of the type suitable for this purpose is a “Mark VPlus Injection System” from Medrad, inc. 271 Kappa Drive, Pittsburgh,Pa. 15238-2870 U.S.A. Other examples include but are not limited to thefollowing: a pressure signal generated within the catheter or in itsdistal tip (e.g. piezoelectrically or by another form of energy burstintroduction e.g. AcolysisSystem, ultrasound thrombolysis selectivelysis of fibrin, by Angiosonics Inc., NC, U.S.A.); is by the movement ofan hydrodynamic surface, activated either manually or by a specialmechanism (e.g. catheter used for removing malpositioned or embolizedstents, for example Amplatz Goose Neck Snare GN 500 and Microsnare SK200from Microvena corporation, Minnesota USA and catheters which preventplaque debris from moving downstream); a pressure signal caused by anexternal controlled pressure applied on an organ, transmitted into apressure signal within the vessel; a pressure signal caused by anon-invasive energy transmission into the vessel (e.g. ultrasound) inwhich the artificial pressure/flow signal may be either controlled ormeasured (within the catheter or the vessel).

In one embodiment the signal generator is a pressure signal generator.As contemplated herein the signal generator is a pressure sensor. Inanother embodiment the signal generator is a flow signal generator. Ascontemplated herein the signal generator is a pressure sensor.

In another embodiment the signal generator is a pressure signalgenerator; said signal sensor is a pressure signal sensor; and saidprocessor unit is operative to receive a heart beat signal; andsynchronize receipt of said probe signal with said heart beat signal. Ascontemplated herein, the signal sensor includes at lest two sensingtransducers disposed in spaced apart relation. The signal sensor ismovable between at least two positions relative to said tubular conduitsystem and said processor unit is operative to calculate a pressure wavevelocity from signals received from said two positions. In anotherembodiment the signal sensor includes a signal conditioner. The signalmay be derived from either one of the internally generated waveforms orexcited electronically from a separate signal generator either a standalone unit. A stand alone until is of the type suitable is amultifunction synthesizer model HP 8904A from HP Test and measurementOrganization, a Hewlett-Packard company USA) or integrated within asystem computer, otherwise used for data acquisition and anaylsis. Forexample, an electric impulse generator is shown in FIG. 29.

In another embodiment the pressure signal may originate from an impactmechanism system. Such impact mechanisms are known to those skilled inthe art. For example, the impact mechanisms may be of the spring loadedor electronically activated mechanical impact system types, applyingpressure on either the catheter or on a container attached to it. Asignal generation apparatus (in vitro and in vivo) of the impactmechanism type makes use of a pistol hammer mechanism, where the pistolhammer hits directly on the catheter, lying on a rigid surface, as shownin FIG. 4. The pistol used was a P230 semiautomatic pistol from SigSauer, Switzerland. Alternatively, the same pistol hammer hit the headof a standard 5 ml syringe, where the syringe was connected to thecatheter through a standard manifold, as shown in FIG. 8.

The artificial pressure flow signal may also be synchronized with heartbeats, either by gating to ECG or to system measurements a(pressure orflow) in which the ECG device measures heart heat signals upon reachinga desired time in the heart beat triggering the artificial pressure flowsignal. The pressure signal dances through a catheter lumen into theblood vessel. The catheter may be a guiding catheter. A guiding catheterof the type suitable for this purpose is a 8F Archer coronary guidingcatheter from Medtronic Internventional Vascular, Minneapolis, U.S.A. Adiagnostic catheter of the type suitable for this purpose is a Siteseerdiagnostic catheter, from Bard Cardiology, U.S.A. A balloon catheter ofthe type suitable for this purpose is a Supreme fast exchange PTCAcatheter by Biotronik GMBH & Co, U.S.A. It will be appreciated by thoseskilled in the art that almost every hollow type catheter may be used.The presence of occlusion or aneurysm downstream creates reflection ofpressure and flow waves. By extracting data of the reflected pressurewaves, originated in the occluded site, the location and degree ofocclusion can be determined using signal processing methods.

Additionally, the system can also be adopted for use in othernon-biological conduits, having a pulsatile flow within, such as waterpipes through which pulsatile flow may be induced for measuring andcharacterizing internal narrowing due to scale deposits. In anotherembodiment said tubular conduit system is a blood vessel system and saidprocessor unit is operative to detect changes in arterialcharacteristics. In one embodiment the tubular conduit system is aurinary vessel system and said processor unit is operative to detectchanges in urinary tract characteristics.

In another embodiment the probe signal is a plurality of discretesignals; said processor unit is operative to sample said discretesignals and receive pressure wave velocity data. The processor unit isoperative to perform a single pressure function using said discretesignals and said pressure wave velocity data. The processor unit whenperforming said single pressure function is opeative to calculate anallpass value and a cepstrum value from said minimum phase component;separate a regular part and a singular part of said cepstrum value,where said singular part and said regular part from said pressure wave;calculate an exponential function of singular part; evaluate a secondpeak time delay with respect to a forward found in said pressure signal;evaluate a coefficient by calculation of a second peak amplitude todetermine an arterial characteristic; evaluate a location of saidarterial characteristic. The processor unit is operative to receive aforward pressure wave signal from a first transducer and a probe signalrepresented by a plurality of discrete signals sampled overtime. Theprocessor until is operative to perform a dual pressure function.

In another embodiment said processor until when performing said dualpressure function is operative to: calculate an allpass component andcepstrum component of a minimum phase component of said forward pressurewave signal received from said signal sensor; apply an inverse filteringof said forward pressure wave signal; apply smoothing by a B-splinefunction; detect a forward peak location by a global maximumcalculation; receive a threshold value; detect a second peak location bycomparison with said threshold, where said threshold is derived from aforward peak maximum value and minimum size of a characteristic;evaluate a second peak time delay with respect to said forward peak;evaluate a reflection coefficient by calculating a forward and reflectedpeak area; and evaluate a location of said characteristic. The processorunit is operative to calculate a pressure wave velocity from a pressurewave sensed by said first and second transducers. In another embodimentthe processor unit includes an analog to digital convertor. In anotherembodiment the processor unit is further operative to ascertain andassign a value corresponding to the location and size of saidcharacteristic of said tubular conduit.

This invention provides a processor apparatus for detecting, locatingand characterizing changes in a tubular conduit system within a livingbody for transferring fluids for use with a signal generator configuredto transmit into said tubular conduit a probe signal that changes inresponse to encountering changes in said tubular conduit system and asignal sensor operative to receive said probe signal followingtransmission into said tubular conduit system, said processor apparatuscomprising: a processor unit operatively connected to said signalsensor; a program for controlling the processor unit; said processorunit operative with said program to receive said probe signal followingtransmission through said tubular conduit system: identify changes insaid probe signal; detect characteristics of said tubular conduitsystem, said characteristics of said tubular conduit system beingderived from changes in said probe signal; recognize and assign a labelsaid characteristic of said tubular conduit said system; and ascertainand assign a value corresponding to the location and size of saidcharacteristic of said tubular conduit.

In one embodiment the processor unit is operative to select a methodfrom a plurality of methods to identify changes in said probe signal andtherefrom detect changes in said tubular conduit system. As contemplatedherein, the processor unit is operative to detect aneurysms, stenosis,and/or arterial occlusions. In another embodiment, the tubular conduitsystem is a blood vessel system and said processor unit is operative todetect changes in arterial characteristics.

In another embodiment, the processor unit is operative to perform asingle pressure function using said discrete signals and said pressurewave velocity data. In another embodiment, the processor unit whenperforming said single pressure function is operative to calculate anallpass value and a cepstrum value from said minimum phase component. Inanother embodiment, the processor unit when performing said singlepressure function is further operative to separate a regular part and asingular part of said cepstrum value, where said singular part and saidregular part form said pressure wave. In another embodiment, theprocessor until when performing said single pressure function is furtheroperative to calculate an exponential function of singular part. Inanother embodiment, the processor unit when performing said singlepressure function is further operative to evaluate a second peak timedelay with respect to a forward found in said pressure signal. Theprocessor until when performing said single pressure function is furtheroperative to evaluate a coefficient by calculation of a second peakamplitude to determine an arterial characteristic. The processor unitwhen performing said single pressure function is further operative toevaluate a location of said arterial characteristic.

In another embodiment the signal generator is a pressure signalgenerator, and said signal sensor is a pressure signal sensor; saidprocessing unit is operative to receive a heart beat signal; andsynchronize receipt of said probe signal with said heart beat signal. Inanother embodiment the probe signal is a plurality of discrete signals;said processor unit is operative to sample said discrete signals andreceive pressure wave velocity data.

In one embodiment the signal sensor includes two sensing transducersdisposed in spaced apart relation and said processor unit is operativeto receive a forward pressure wave signal from a first transducer and aprobe signal represented by a plurality of discrete signals sampledovertime. The processor until is operative to calculate a pressure wavevelocity from a pressure wave sensed by said first and secondtransducers. The processor unit is operative to perform a dual pressurefunction. In another embodiment, the signal sensor is movable between atleast two positions relative to said tubular conduit system and saidprocessing unit is operative to calculate a pressure wave velocity fromsignals received from said two positions.

In one embodiment the processor unit when performing said dual pressurefunction is operative to calculate an allpass component and cepstrumcomponent of a minimum phase component of said forward pressure wavesignal received from said signal sensor. In another embodiment, theprocessor until when performing said dual pressure function is furtheroperative to apply an inverse filtering of said forward pressure wavesignal. The processor until when performing said dual pressure functionis further operative to apply smoothing by a B-spline function. Theprocessor until when performing said dual pressure function is furtheroperative to detect a forward peak location by a global maximumcalculation. The processor unit when performing said dual pressurefunction is further operative to receive a threshold value. Theprocessor unit when performing said dual pressure function is furtheroperative to detect a second peak location by comparison with saidthreshold, where said threshold is derived from a forward peak maximumvalue and minimum size of a characteristic. The processor unit whenperforming said dual pressure function is further operative to evaluatea second peak time delay with respect to said forward peak. Theprocessor unit when performing said dual pressure function is furtheroperative to evaluate a reflection coefficient by calculating a forwardand reflected peak area. The processor unit when performing said dualpressure function is further operative to evaluate a location of saidcharacteristic. The processor unit is operative to calculate a pressurewave velocity from a pressure wave sensed by said first and secondtransducers.

This invention provides a method for using a computer to detect, locateand characterize changes in a tubular conduit system within a livingbody for transferring fluids wherein said computer is operativelyconnected to a signal generator configured to transmit into said tubularconduit a probe signal that changes in response to encountering changesin said tubular conduit system and a signal sensor operative to receivesaid probe signal following transmission into said tubular conduitsystem, said method comprising the steps of: receiving said probe signalfollowing transmission through said tubular conduit system: identifychanges in said probe signal; detecting characteristics of said tubularconduit system, said characteristics of said tubular conduit systembeing derived from changes in said probe signal; and recognizing andassigning a label said characteristic of said tubular conduit saidsystem. In one embodiment the method includes the steps of ascertainingand assigning a value corresponding to the location and size of saidcharacteristic of said tubular conduit. The method further includesselecting a process from a plurality of processes identifying changes insaid probe signal and therefrom detecting changes in said tubularconduit system.

In one embodiment the tubular conduit system is a blood vessel system,said method further including detecting changes in arterialcharacteristics, detecting aneurysms, detecting stenosis, and/ordetecting arterial occlusions.

In one embodiment the signal generator is a pressure signal generator,and said signal sensor is a pressure signal sensor; said methodincluding receiving a heart beat signal; and synchronizing receipt ofsaid probe signal with said heart beat signal. In another embodiment,the probe signal is a plurality of discrete signals; said methodincluding sampling said discrete signals and receiving pressure wavevelocity data. The method may include the steps of performing a singlepressure function using said discrete signals and said pressure wavevelocity data. Performing step includes the step of calculating anallpass value and a cepstrum value from said minimum phase component.Further, performing step includes the step of separating a regular partand a singular part of said cepstrum value, where said singular part andsaid regular part form said pressure wave. The step of calculating anexponential function of singular part. In another embodiment, theperforming step includes the step of evaluating a second peak time delaywith respect to a forward found in said pressure signal. In anotherembodiment the performing step includes the step of evaluating acoefficient by calculation of a second peak amplitude to determine anarterial characteristic. In another embodiment the performing stepincludes the step of evaluating a location of said arterialcharacteristic.

In one embodiment the signal sensor includes two sensing transducerdisposed in spaced apart relation, said method includes the step ofreceiving a forward pressure wave signal from a first transducer and aprobe signal represented by a plurality of discrete signals sampledovertime. In another embodiment the method further includes the step ofcalculating a pressure wave velocity from a pressure wave sensed by saidfirst and second transducers. A dual pressure function may be performed.In another the signal sensor is movable between at least two positionsrelative to said tubular conduit system, said method including the stepof calculating a pressure wave velocity from signals received from saidtwo positions.

In another embodiment, the performing step includes the step ofcalculating an allpass component and cepstrum component of a minimumphase component of said forward pressure wave signal received from saidsignal sensor. In another embodiment the performing step includes thestep of applying an inverse filtering of said forward pressure wavesignal. In another embodiment, the performing step includes the step ofapplying smoothing by a B-spline function. In another embodiment theperforming step includes the step of detecting a forward peak locationby a global maximum calculation. In another embodiment the performingstep includes the step of receiving a threshold value. In anotherembodiment the performing step includes the step of detecting a secondpeak location by comparison with said threshold, where said threshold isderived from a forward peak maximum value and minimum size of acharacteristic. In another embodiment the performing step includes thestep of evaluating a second peak time delay with respect to said forwardpeak. In another embodiment the performing step includes the step ofevaluating a reflection coefficient by calculating a forward andreflected peak area. In another embodiment the performing step includesthe step of evaluating a location of said characteristic. In anotherembodiment the performing step includes the step of calculating pressurewave velocity from a pressure wave sensed by said first and secondtransducers.

With reference to the Figures for purposes of illustration, reference isnow made to FIGS. 1 and 2. FIG. 1 is a schematic isometric view of asystem for characterizing blood vessel occlusions, vascular bed andblood vessel walls constructed and operative in accordance with oneembodiment of the present invention. FIG. 2 is a schematic functionalblock diagram illustrating the details of the system 1 of FIG. 1.

The system 1 includes a signal conditioner 23, such as a model TCB-500control unit commercially available from Millar Instruments, a RadiPressure Wire Interface Type PWI10, Radi Medical Systems, Upsala, orother suitable signal conditioner. The signal conditioner 23 isoperatively connected to the pressure sensor 4 for amplifying thesignals of the pressure sensor. The system 1 further includes an analogto digital (A/D) converter 28 connected to the signal conditioner 23 forreceiving the conditioned analogs signals therefrom. The system 1 alsoincludes a signal analyzer 20 connected to the A/D converter 28 forreceiving the digitized conditioned pressure signals from the A/Dconverter 28. The signal analyzer 20 includes a computer 25, andoptionally a display 21 connected to the computer 25 for displaying textnumbers and graphs representing the results of the calculationsperformed by the computer 25 and a printer 26 operatively connected tothe computer 25 for providing hard copy of the results for documentationand archiving. The A/D converter 28 can be a separate unit or can beintegrated in a data acquisition computer card installed in the computer25 (not shown). The computer 25 processes the pressure data which issensed by the pressure sensors 4 and acquired by the A/D converter 28 orthe data acquisition card (not shown) and generates textual, numericaland/or graphic data that is displayed on the display 21.

Another embodiment of the system 1 is a single unit containing both PSGand data acquisition, analysis and display, with or without correlationto ECG input. The system 1 includes a pressure catheter (or a pressureguidewire) 2 having a pressure sensor 4 attached thereto for measuringthe pressure inside a blood vessel. In an exemplary embodiment, thepressure catheter 2 can be the 3F “one pressure sensor” model SPC-330Acommercially available from Millar Instruments Inc., TX, U.S.A., or anyother pressure catheter suitable for diagnostic or combineddiagnostic/treatment purposes such as the 0.014″ guidewire mountedpressure sensor product number 12000 from Radi Medical Systems, Upsala,Sweden, or Cardiometrics Wave Wire pressure guidewire from CardiometricsInc. an Endsonics company of CA, U.S.A.

It will be appreciated by those skilled in the art that the pressureand/or flow wave signals described herein each have a pressure and flowwave component. Such waves also produce distension of the vessel wall.For purposes of understanding, distension characteristics in general aremost commonly visualized by observing a snake swallow and digest a largeanimal. Therefore, a pressure sensor, flow wave sensor or changes in thecross-sectional area or diameter measured over time can be used tocollect data in connection with the procedures of the present invention.

Thus, another embodiment of system 1, includes a pressure or flow wavegenerator and a flow wave sensor 4. A flow wave sensor of the typesuitable for this purpose are the Flowwire catheters manufactured byEndosonics Corporation, U.S.A. in which the system uses dopplerultrasound technology to accurately measure arterial blood flow velocityproviding functional lesion assessment. Such device provide formeasurements suitable for the procedures of the present invention assold commercially or preferably when modified to allow for frequencyincreases to 200 Hz.

Accordingly another embodiment of the system 1 includes a pressure orflow wave signal generator and signal sensor adapted to changes in thecross-sectional diameter of the vessel caused by distension. A devicesuitable for this purpose is an intravascular ultrasound device of thetype sold by Endosonics, USA having IVUS, Visions five 64 cathetercatalog number 82700 together with IVUS Oracle In vision TM imagingsystem catalog number S7700470-inv. The IVUS data is measured while anartificial flow/pressure signal is introduced into the vessel. Otherintravascular ultrasound systems provide diameter measurement at higherfrequency and may be more easily processed at shorter distances ofocclusion from sensor. A device of this type is an IRL VasoScan system,available from Intravascular Research Limited, Britain. The IRLVasoScan™ Pullback Sensor is an elegant simple innovation thatfacilitates lesion length measurement. AS the catheter is passed throughthe pullback device, the sensor measures movement both forward andbackward. The user manually controls the device without sacrificingmeasuring accuracy. Measurements are displayed digitally on a systemscreen.

In another embodiment the signal generator is a pressure or flow signalgenerator and said signal sensor is a non-invasive high accuracy echotracking Radio Frequency—ultrasound. A device this type is Model No.CFM-800c Ultrasound scanner produced by VINGMED, Norway, a GeneralElectric company. This type of measurement provides basically the rawultrasound data, prior to pre-processing and image processing. Thereforeit may be available from other ultrasound scanners with some hardwareand or software work. Other devices may include Model No. HP SONOS 5500Cardiovascular Ultrasound System from Hewlett Packard, USA or Model No.HDI-5000 system from ATL, Seattle, USA (a Phillips company). Thenon-invasive ultrasound data is measured externally while an artificialflow/pressure signal is introduced into the vessel.

Reference is now made to FIG. 3. FIG. 3 is a schematic cross sectionillustrating the positioning of the guiding or diagnostic catheter 3through which the pressure signal travels, relative to an obstructionand vascular bed within an occluded blood vessel during operation of thesystem 1 of FIG. 1.

The guiding catheter (or diagnostic catheter) 3 together with thepressure catheter or guidewire 2, to which the pressure sensor 4 isattached, are inserted into the vascular system of the patient using astandard connector 8 and standard methods and moved to reach the bloodvessel of interest. FIG. 3 illustrates a cross section of an artery 30having an arterial wall 32. The artery 30 also includes a stenoticobstruction 34 obstructing the blood flow through the artery 30. Thedegree of obstruction is defined as the ratio of the cross-sectionalarea of the stenotic region to the cross-sectional area of theunobstructed artery (not shown). The cross-sectional area of thestenotic region is the cross-sectional open area at the narrowest partof the occlusion. The obstruction distance is defined as the distancebetween the measuring point of the pressure sensor 4 to the narrowestcross-section of the obstruction (not shown). In some of the methodspresented below, two pressure measurements are required. In those cases,the proximal measurement my be collected using a pressure transducer 7(e.g. Baxter Model PX272, pressure monitoring kit from Baxter HealthcareCorporation, Ca, U.S.A.), connected to the guiding catheter of system 1via the connector 8, or a second intravascular pressure transducer, orthe two single pressure sensors may be mounted on a mutual wire orcatheter (e.g. Millar 2.5F dual sensor model SPC-721, Millar InstrumentsInc., TX, U.S.A.).

The pressure catheter 2 is advanced within the artery 30 proximal to theobstruction 34 in the direction of the arterial blood flow indicated bythe arrow labeled 36, or opposite. PSG 5 creates a pressure signal,either synchronized with natural beats (ECG) or not, represented by thearrow 39 labeled P₁. P_(M)(t) is the combination of the incidentpressure wave, and the reflected pressure wave P_(R) (pressure signalreflected by the stenosis 34), represented by the arrow 40 labeledP_(R), which was reflected from the obstruction at a time (t−τ), whereinτ is the time delay between the forward pressure wave and the reflectedpressure wave, read by the transducer. Following, several methods willbe presented, serving for distinguishing P₁ from P_(R) while measuringP_(M)(+), calculating τ and while knowing PWV determining distance tothe reflecting site (either stenosis or VB or both). Several methods forcalculating the location and reflection coefficient R_(F) of thestenosis are presented. Several methods for calculating the pressurewave velocity are presented. The main geometrical parameter of astenosis is stenosis severity As/Ao. Here As is the minimum opencross-sectional area of the stenosis and Ao is the nominalcross-sectional area of the unobstructed vessel. In one model forpressure drop across stenosis, suggested by Young and Tsai (Young D. F.and Tsai F. Flow characteristics in model of arterial stenoseses -II.Unsteady flow. J.Biomechanics 6, 547-559, 1973.), allows to relatereflection coefficient to geometrical parameters of the stenosis,characteristics of the excited pressure wave and input impedance of theblood vessel. The related equations may be found in the work N.Stergiopulos, M. Spiridon, F. Pythoud, J. J. Meister. On the wavetransmission and reflection properties of the stenosis. J.Biomechanics,v.29, No.1, pp. 31-38, 1996. In the general case, stenosis severityAs/Ao and stenosis length L may be found only if reflection coefficientis known for different frequencies. Therefore, in the general case thereflection of the exciting pressure signal containing differentfrequencies must be measured. Another possible way is to determine oneof the geometrical parameters (stenosis length or stenosis severity)from QCA. The other parameter may be calculated from the measuredreflection coefficient.

For short lesions the reflection coefficient is directly related tostenosis severity and the pressure excitation signal. The same principleholds for flow and velocity measurements. A good approximation of thereflection coefficient, based on the linearized flow theory is given bythe following relation: R_(F)=(Ao−As)/(Ao+As). This relationship holdsfor short distances where signal attenuation is not significant. Forlong range stenoses the calculation should correct for the attenuationof the pressure excitation signal and its reflections.

The present invention discloses a device and a method for a quantitativedetermination of the elastic properties of blood vessels forcharacterizing, inter alia, the real part of the complex Young modulus,the distensibility and the compliance of lesioned and non-lesioned partsof blood vessels. The derived elastic properties may be further used todetermine the degree of calcification of lesioned and non-lesioned partsof blood vessels. These parameter values can be calculated and reportedin absolute terms as a ratio of the relevant parameter value in thelesion region to the parameter value in a non-lesion region of the samepatient. Alternatively, the system may calculate and report a ratio ofthe relevant parameter determined in the lesion region of the patient toa “standard” average value of the relevant parameter as measured in agroup of healthy people with similar physiology (age group, gender,vessel type, etc.). In the second alternative, the system will includemeans for storing such standard average values of the relevantparameters such as a data-based stored in a suitable storage deviceincluded in the system (not shown).

The determination of the elastic properties of an artery is based oncalculating the phase velocity of the pressure wave. Reference is nowmade to FIGS. 5-7. FIG. 5 is a schematic diagram representing anin-vitro experimental apparatus constructed and operative fordetermining flow characteristics in simulated non lesioned and lesionedblood vessels, in accordance with an embodiment of the presentinvention. FIG. 2 is a schematic functional block diagram illustratingthe functional details of a system including the apparatus of FIG. 5 andapparatus for data acquisition, analysis and display.

Reference is now made to FIG. 5. The system 41 includes the system 51.The system 41 also includes a signal conditioner 23. A conditioner ofthe type suitable for this purpose is a model TCB-500 control unitcommercially available from Millar Instruments, or any suitable signalconditioner. The signal conditioner 23 is operatively connected to thepressure sensors 24A and 24B for amplifying the signals of the pressuresensors 24A and 24B. The system 41 further includes an analog to digital(A/D) converter 28 connected to the signal conditioner 23 for receivingthe conditioned analog signals therefrom. The system 41 also includes asignal analyzer 20 connected to the A/D converter 28 for receiving thedigitized conditioned pressure signals from the A/D converter 28. Thesignal analyzer 20 includes a computer 25, a display 21 connected to thecomputer 25 for displaying text numbers and graphs representing theresults of the calculations performed by the computer 25 and a printer26 operatively connected to the computer 25 for providing hard copy ofthe results for documentation and archiving. The A/D converter 28 can bea separate unit or can be integrated in a data acquisition computer cardinstalled in the computer 25 (not shown). The computer 25 processes thepressure data which is sensed by the pressure sensors 24A and 24B andacquired by the A/D converter 28 or the data acquisition card (notshown) and generates textual, numerical and graphic data that isdisplayed on the display 21.

The fluidics system 51 of FIG. 6 is a recirculating system for providingpulsatile flow. The system 51 includes a pulsatile pump 42. A pump ofthe type suitable for this purpose is a model 1421A pulsatile bloodpump, commercially available from Harvard Apparatus, Inc., Ma, U.S.A.,however other suitable pulsatile pumps can be used. The pump 42 allowscontrol over rate, stroke volume and systole/diastole ratio. The pump 42recirculates distilled water from a water reservoir 15 to a waterreservoir 14.

The system 51 further includes a flexible tube 43 immersed in a waterbath 44, to compensate for gravitational effects. The flexible tube 43is made from Latex and has a length of 120 cm. The flexible tube 43simulates an artery. The flexible tube 43 is connected to the pulsatilepump 42 and to other system components by Teflon tubes. All the tubes insystem 51 have 4 mm internal diameter. A bypass tube 45 allows flowcontrol in the system and simulates flow partition between bloodvessels. A Windkessel compliance chamber 46 is located proximal to theflexible tube 43 to control the pressure signal characteristics. AWindkessel compliance chamber 47 and a flow control valve 48 are locateddistal to flexible tube 43 to simulate the impedance of the vascularbed. The system 51 of FIG. 5 further includes an artificial stenosismade of an artificial stenosis section 55, inserted within the flexibletube 43. The tube section 55 is made from a piece of Teflon tubing. Theinternal diameter 52 (not shown) of the artificial stenosis 55 may bevaried by using artificial stenosis sections fabricated separately andhaving various internal diameter. The external diameter of all theartificial stenosis section 55 is 4 mm. Thus, various degree of crosssectional area reduction (40%-95%) can be generated in the distal partof the flexible tube 43, for simulating various degrees of stenosis.

Reference is now made to FIG. 7, which is a schematic cross sectionalview illustrating a part of the fluidics system 51 in detail. Pressureis measured along the flexible tube 43 using a pressure measurementsystem including MIKRO-TIP pressure catheters 58 and 59, such as themodel SPR-524 pressure catheter, connected to a model TCB-500 controlunit, both commercially available from Millar Instruments Inc., TX,U.S.A. The catheters 58 and 59 are inserted into the flexible tube 43via the connector 10, connected at the end of the flexible tube 43. Thecatheters 58 and 59 include pressure sensors 24A and 24B, respectively,for pressure measurements. It is noted that, other catheters or guidewires made by different manufacturers may also be used, such as variouspressure measurement guide wires of the type commercially available fromRadi Medical Systems AB, Upsala, Sweden, or from Cardiometrics, anEndosonics company of CA, U.S.A.

The end of catheter 3 is inserted into the flexible tube 43 via aconnector 9. The other end is connected to a pressure signal generatorunit 5, which creates pressure impulse. The pressure wave advance in thefluid through the catheter 56 to vessel 43. When the pressure wavereaches the artificial stenosis 55, reflection of the pressure wave iscreated. The pressure sensors 24A, 24B measure the original pressurewave and the reflections from the artificial stenosis, and otherreflections of the system such as the reflection from the right flexibletube edge 57. A fluid filled pressure transducer 7 is connected to thesystem 51 via the connector 9, when additional pressure readings areneeded, or in place of a second intravascular pressure transducer, whentwo pressure measurements are of interest.

The system 51 of FIG. 6 also includes a flowmeter 11 connected distal tothe flexible tube 43 and a flow meter 12 connected to the bypass tube45. The flowmeters 11 and 12 are operatively connected to the A/Dconverter 28. The flowmeters 11 and 12 are model 111 turbine flow metersof the type commercially available from McMillan Company, TX, U.S.A.However, other commercial available flow sensors may be used.

EXPERIMENTAL DETAILS SECTION

Data acquisition and analysis:

Data acquisition was performed using a PC (Pentium 586) with an E seriesmultifunction I/O board 28 model PC-NIO-16E-4 of the type commerciallyavailable from National Instruments Inc., TX, U.S.A. The I/O board wascontrolled by a Labview graphical programming software, commerciallyavailable from National Instruments Inc., TX, U.S.A. 10 sec interval ofpressure and flow data were sampled at 5000 Hz, displayed during theexperiments on the monitor and stored on hard disk. Analysis wasperformed offline using Matlab version 5 software, commerciallyavailable from The MathWorks, Inc., MA, U.S.A.

System Implementation Methods and Procedures:

The system uses various methods to detect the existence, location andseverity of a stenosis or aneurysm in a blood vessel. The methods arebased on four main data analysis procedures which are describedhereinbelow. Other data analysis procedures may be developed based onthe principles hereinbelow presented. The choice between proceduresdepends on the signal length and distance from the lesioned area. Thesetwo parameters define the time of the reflection within the signal theamount of separation between the forward and backward signal serves toselect the proper procedure. In the data presented hereinbelow, acquiredon the in-vitro system presented in FIGS. 4-6, and with pressure wavevelocity of 14 m/sec, three different cases were defined: far distance(over 40 cm), mid distance (10-40 cm) and short distance (2-10 cm)stenoses. Usually, far and mid distance stenoses were found using theProcedure 1 presented below. Short distance stenosis were identifiedusing both Procedure 1 and 2 presented below. As well, in vivo pig datais included, identifying induced occlusions.

PROCEDURE 1 The Dual Pressure Function

The following procedure analyzeD a downstream pressure measurement,composed of both forward and reflected waves, by a priori knowledge ofthe forward wave. It was determined from:

a. an upstream measurement, either simultaneously (additionaltransducer) or non simultaneously [moving the transducer] or

b. a priori knowledge of forward pressure wave, resulting from knownpressure excitation with known catheter

Input data required for the procedure:

1. The forward pressure wave, w[n].

2. The pressure measured by a downstream sensor—s[n], n=1, . . . N,where N is the number of samples.

Assumptions:

1. All measured signals are discrete-time signals.

2. The vessel is a linear, stable and time-invariant causal system.

3. The time resolution of the linear system is much less then the timedelay of the reflected pressure wave.

4. Reflection coefficient is a constant.

5. Exciting signal (forward pressure wave) is known.

6. The pressure wave velocity V is known. The pressure wave velocity maybe calculated with Procedure 3, or assumed to be known from previoustest data. It also was known from anatomic data, according to exactvessel, age and clinical situation.

Experiment setup:

Procedure description:

The following relationship holds:

s[n]=w[n]+b[n−m]=w[n]{circle around (×)}(δ[n]+r*g[n−m]);  (1)

where,

{circle around (×)}—is the discrete convolution operator;

s[n]—is the measured pressure wave;

w[n]—is the forward pressure wave;

b[n]=r*g[n]{circle around (×)}w[n]—is the reflected pressure wave;

d—is the distance between the downstream sensor to the stenosis;

g[n]—is the response of the vessel in 2d length (to the stenosis andback);

r—is the reflection coefficient;

m=round (2*d/v)—is the time delay (in samples) of the reflected pressurewave;

v—is the pressure wave velocity;

Δ—is the distance between transducers.

Using the commutative property of the convolution, Equation (1)describes a digital linear filter: δ[n] + r * g[n − m]w[n]s[n]

where w[n] represents the impulse response of this filter.

The parameters r and m of the reflected wave describe the stenosis sizeand location. Therefore, in order to evaluate the stenosis we need toevaluate the reflected wave parameters. In the common case, it isimpossible to detect the reflected wave and evaluate its parameters byinspecting the signal s[n]. In order to get information about thereflected wave inverse filtering to the measured pressure wave wasapplied:

δ[n]+r*g[n−m]=w ⁻¹ [n]{circle around (×)}s[n].

The result is a function including two peaks representing the forwardand reflected pressure wave and having different amplitudes. The firstmaximum is equal to 1 and the second one is r. The time differencebetween the peaks is the reflected pressure wave delay.

As the output signal s[n] includes measurement noise, smoothing filterh[n] should be applied prior to the inverse filtration:

h[n]{circle around (×)}(w ⁻¹ [n])=h[n]{circle around(×)}(δ[n]+r*g[n−m])=h[n]+r*(h[n]{circle around (×)}g[n−m])

Since it was assumed that w[n] is known, the Minimum-Phase/Allpassdecomposition was obtained by iterative procedure described by TarasovR. P. (Comput.Maths.Math.Phys., Vol.32,No.10,pp.1373-1390,1992), Thecomputation of functions in the algebra of formula polynomials andmultidimensional digital signal processing procedures.

w[n]=u[n]{circle around (×)} exp (k[n]), where

u[n]—is the Allpass component;

exp (k[n])—is the Minimum-Phase component;

k[n]—is the cepstrum of a Minimum-Phase component.

Once u[n] and k[n] are evaluated, the inverse filter of the measuredpressure wave s[n] is h[n]:

h[n]+r*(h[n]{circle around (×)}g[n−m])=h[n]{circle around(×)}(u[−n]{circle around (×)} exp (−k[n]{circle around (×)}s[n])  (2).

For final smoothing purpose B-spline was used.

Procedures steps:

Step 1: Input: w[n]. The allpass component u[n] and the cepstrum k[n] ofthe minimum-phase component of the forward wave w[n] was calculated.

Step 2: inverse filtering by expression (2) was applied

Step 3: smoothing by B-spline was applied

Step 4: the forward peak location by global maximum calculation wasdetected

Step 5: the reflected peak location was detected by comparison with thethreshold that depends on forward peak maximum M_(f) and minimumstenosis size of interest.

Step 6: the reflected peak time delay was evaluated with respect toforward peak by reflected peak shift m calculation: τ=m*f, where f isthe sampling frequency

Step 7: the reflection coefficient r was evaluated by calculating theforward and the reflected peak area. Reference is now made to FIG. 17.FIG. 17 presents the result of Procedure 1, where the first peakrepresents the input pressure pulse and the second peak represents thereflected pressure wave. The ratio of the area under those peaks servesto estimate the severity of the stenosis or aneurysm, according to thedefinition presented hereinabove.

Step 8: the stenosis location was evaluated by: d=v*τ/2

In the above procedure, s(n) represents a pressure measurement at pointB, as demonstrated in FIG. 11. W(n) was derived as:

1. A second pressure measurement, derived by a second pressure sensor,located upstream at location A—presented in Method 6.

2. A second pressure measurement derived with the same pressure sensor,moved to an upstream location, designated A—presented in Method 4.

3. A prior knowledge of the input signal (excitation signal and transferfunction of the catheter)—presented in Method 3.

4. The initial part (in the time domain) of the pressure signal, s(n),for a long range stenosis, where a complete separation of the forwardand backward signals occurs—presented in Method 2.

PROCEDURE 2 Single Pressure Function

Input data required for the procedure:

1. Pressure versus time function Pa[n]=Pa(Δt*n), n=1, . . . N,$\frac{1}{\Delta \quad t}$

is the sampling frequency.

2. Pressure wave velocity. The velocity was assumed to be known fromprevious test data, or derived according to Procedure 4, presentedbelow.

Procedure description:

If the exciting signal was unknown, the reflected wave parameters wereevaluated by separating the regular ln w[n] and the singular p[n] of theln s[n] where

lns[n]≡k_(s)≈ln w[n]+p[n] and lnw[n]≡k[n],

p[n]= $\begin{matrix}{{{p\lbrack n\rbrack} = {\sum\limits_{i = 1}^{j}{\left( {- 1} \right)^{i + 1}*r^{i}*{{\delta^{i}\left\lbrack {n - {i*m}} \right\rbrack}/i}}}},{\delta^{i + 1}\lbrack n\rbrack}} \\{{= {{\delta^{i}\lbrack n\rbrack} \otimes {\delta \left\lbrack {n - m} \right\rbrack}}},{{\delta^{0}\lbrack n\rbrack} \equiv {{\delta \lbrack n\rbrack}.}}}\end{matrix}$

where

s[n]=w[n]+b[n−m]=w[n]{circle around (×)}(δ[n]+r*g[n−m] is the measuredpressure wave;

Procedure steps:

Step 1: the allpass component u_(s)[n] and the cepstrum k_(s)[n] of theminimum-phase component: s[n]=u_(s)[n]{circle around (×)} exp (k_(s)[n]was calculated.

Step 2: the regular lnw[n] and the singular p[n] part of the k_(s)[n]were separated

Step 3: the exponential function of the p[n]: q[n]=exp p[n]wascalculated

Step 4: the reflected (second) peak time delay τ with respect to forwardpeak: τ=m*f, where f- is the sampling frequency was evaluated

Step 5: the reflection coefficient r by calculation of the reflectedamplitude, or area (as demonstrated in FIG. 17) was evaluated.

Step 6: the stenosis location by: d=v*τ/2 was evaluated

PROCEDURE 3 Pressure Wave Velocity with Two Pressure Transducers

Simultaneous pressure measurements with two pressure transducers wasdetermined as follows: the pressure wave velocity was derived as DL/Dt,where DL is the distance between the transducers and Dt is the timedelay between corresponding points on the pressure-time curves asmeasured by the two transducers (for example, Dt at a time delay betweenpressure maxima may be used or alternatively, one may choose the timedelay between points at which the pressure attains a fixed, arbitrarilychosen, percentage of the full range of the pressure curve (e.g. 10%)).The measured pressure rises very fast and in most cases it reaches itsmaximum before the reflected wave has had time to overlap the forwardpressure wave. It is known, that the PWV in arterial segment increaseswith pressure, which is an indication of gradual stiffening of theartery with pressure. By using well established viscoelastic arterialmodels, the analysis of the PWV for several specified percentage of fullrange of the pressure enables one to computer the stiffness of thevessel wall.

PROCEDURE 4 Pressure Wave Velocity with One Pressure Transducer

PMV is calculated using a single pressure or flow transducer, measuringreflection time at two sites Ds cm apart. The reflection time, at eachsite, is found using one of the single pressure transducer methodsdescribed hereinbelow. Dt is the difference between the measuredreflection times at these two points. The pressure wave velocity is thencalculated as: PMV=2·Ds/Dt.

METHOD NO. 1: Single pressure sensor—unknown input signal

Reference is now made to FIG. 9. A single pressure sensor 4 is insertedinto the blood vessel of interest 30 and positioned at point A. Pressurepulse is applied by the pulse generator 5 and data of pressure versustime Pa(t), at point A, are obtained. The applied pressure pulse isassumed to be unknown, or the applied pressure pulse is known but thetransfer function of the catheter is unknown. Subsequently, the inputpressure signal entering the blood vessel is unknown.

Data analysis

The system uses the single pressure function procedure (Procedure 2) todetect the existence and location of a stenosis, aneurysm or vascularbed.

Output Results

1. Location of stenosis, aneurysum or vascular bed.

2. Stenosis or aneurysm severity.

3. Pressure wave velocity. The velocity is calculated using Procedure 4or assumed to be known from previous test data.

In-Vivo Experimental Results

Reference is now made to FIG. 10. In-vivo experiment was performed on apig carotid using a single pressure sensor 91 inserted into the vesselvia a standard 8F catheter 93. An artificial occlusion 92 was appliedabout 5 cm distal to the pressure sensor 91, created by an externaloccluder balloon (Vascular Occluder, IN VIVO METRIC, California, U.S.A.)causing blood vessel lumen diameter reduction to about ⅔ of the originaldiameter (about 50% lumen area reduction)—estimation has been performedbased on angiographics. An artificial flow/pressure signal has beenintroduced into the catheter using the syringe acted by a pistol hammermechanism described in FIG. 8. An unknown input pressure signal wasapplied. Pressure versus time data measured by the pressure sensor 91are shown in FIGS. 25 and 26.

The two peaks shown in FIG. 26 are the pressure input signal 93, and thereflected pressure signal 94. The data were processed by Procedure 2.FIG. 27 shows the result of the analysis: two major peaks representingthe timing and amplitude of the forward pulse and the reflected pulse.The distance between the two peaks in msec (T) is measured from thegraph. The velocity of the pressure wave was found −5.5 m/sec. Thedistance of the stenosis from the pressure sensor is calculated usingthe velocity and time interval: 0.016×5.6=0.09. The distance to stenosisis therefore 0.09/2=4.5 cm, similar to the distance which was measuredangiographically). The calculated reflection coefficient was found to be0.4. This correlates well with the calculation based onR_(f)=(Ao−As)/(Ao+As) presented hereinabove: Ao=π16 mm², As=π6.25 mm²resulting in a reflection coefficient of 0.44.

METHOD NO. 2: Single Pressure Sensor—Long Range Stenosis

Data Acquisition

The method is described in FIG. 9. A single pressure sensor 4 isinserted into the blood vessel of interest 30 and positioned at point A,upstream the stenosis. The distance between the sensor and the stenosisresult in a separation of the exciting pressure wave (forward wave) andthe reflected wave (backward wave). Pressure pulse is applied by thepulse generator 5 and data of pressure versus time Pa(t), at point A,are obtained.

Data Analysis

The system uses the two pressure function procedure (Procedure 1) todetect the existence and location of stenosis, aneurysm or vascular bed.No prior knowledge of the exciting signal is required. The procedure istaking advantage of the inherent separation of the forward and backwardcomponents of the signal. The procedure is modified to recognize theinput signal, w(n), from the first part of the output signal, and applythe Procedure 1 to the second part of the signals, s(n). The system usesthe method described in FIG. 17 to estimate the severity of stenosis oraneurysm.

Input Data Required for Using the Procedure

1. Pressure versus time function Pa(t), measured by the single sensor 4.

2. Pressure wave velocity. The velocity was calculated using Procedure 4or assumed to be known from previous test data.

Output Results

1. Location of stenosis, aneurysm or vascular bed.

2. Stenosis or aneurysm severity.

In-Vitro Experimental Results

Data were acquired on the in-vitro system described in FIGS. 5-7, with asingle pressure sensor, 24 a, within. FIG. 28 illustrates theapplication of the Procedure 2 on an in-vitro pressure data. The lowerpart of FIG. 28 presents the pressure versus time as measured by thepressure sensor, Pa(t), located at A. The upper part of FIG. 28 presentsthe result of the Procedure 1, where the 2 peaks, of the input pressurewave (P_(I)), and the reflected wave (P_(R)) can be clearly observed.The time interval between the two peaks is calculated from FIG. 28 to be56 msec. Knowing the velocity of the pressure wave, 14 m/sec, allowscalculating the stenosis location: 0.056×14=0.392 m. This is a perfectmatch to the 40 cm distance between the transducer and the stenosis.

METHOD NO. 3: Single Pressure Sensor—Known Input Signal

Data Acquisition

The method is described in FIG. 9. A single pressure sensor is insertedinto the blood vessel of interest 30 and positioned at point A. Pressurepulse is applied by the pulse generator 5 and data of pressure versustime Pa(t), at point A, are obtained. The applied pressure signal iscontrolled and known from the pulse generator 5. The transfer functionof the catheter is assumed to be known. Therefore the input pressuresignal entering the blood vessel is known.

Data Analysis

The system uses the dual pressure function procedure (Procedure 1) todetect the existence and location of stenosis, aneurysm or vascular bed.The system uses the method described in FIG. 17 to estimate the severityof stenosis or aneurysm.

One could refer to the in-vitro example discussed in Method 6, andpresented in FIG. 19, as a demonstration of the actual method, where theupstream pressure signal is considered as a known input.

Input Data Required for Using the Procedure

1. Pressure versus time function Pa(t), measured by the sensor 4.

2. Pressure wave velocity. The velocity is assumed to be known fromprevious test data or calculated using Procedure 4.

3. Catheter transfer function. The pressure versus time transferfunction is assumed to be known from previous test results.

4. Exciting signal (forward pressure wave). The signal magnitude,duration and shape are controlled and known by the pressure generator 5.

Output Results

1. Location of stenosis, aneurysm or vascular bed.

2. Stenosis or aneurysm severity.

METHOD NO. 4: Single Pressure Sensor—Two Measuring Sites

Data Acquisition

The method is described in FIG. 18. A single pressure sensor is insertedinto the blood vessel of interest and positioned at point A. Pressurepulse is applied by the pulse generator 5 and data of pressure versustime Pa(t), at point A, are obtained. The pressure sensor is now moveddownstream, by a known distance L and positioned at point B. Thepressure generator 5 generates a similar pressure pulse, and data ofpressure versus time, Pb(t), are obtained.

Data Analysis

The system uses the dual pressure function procedure (Procedure 1)described above to detect the existence and location of stenosis,aneurysm or vascular bed. The system uses the method described in FIG.17 to estimate the severity of stenosis or aneurysm. One could refer tothe in-vitro example discussed in Method 6, and presented in FIG. 19, asa demonstration of the actual method, where the upstream pressure signalis acquired by the same pressure sensor location in A and the downstreamsignal is acquired by the same pressure sensor moved to B.

Input Data Required for Using the Procedure

1. Pressure versus time measured at location A—Pa(t).

2. Pressure versus time measured at location B—Pb(t).

3. Pressure wave velocity. The velocity is assumed to be known fromprevious test data, or evaluated using the single pressure PWVprocedure.

4. Input signal (forward pressure wave). The signal magnitude, durationand shape are controlled and known by the pressure generator.

Output Results

1. Location of stenosis, aneurysm or vascular bed.

2. Stenosis or aneurysm severity.

METHOD NO.5: Two-Pressure Sensors—Visual Method

Reference is now made to FIG. 11 and 13. Two pressure sensors 4 a and 4b are inserted into the blood vessel 30 of interest via a standardconnector 8 connected to a catheter 3. In another embodiment, thepressure sensors 4 a and 4 b may be mounted on a mutual wire or catheter(e.g. Millar 2.5F dual sensor model SOPC-721, Millar Instruments Inc.,Texas, U.S.A.). In another embodiment, the pressure sensor 4 a may be afluid filled manometer sensor connected to the catheter 3 via theconnector 8. The pulse generator 5 applies a pressure pulse. Data ofpressure versus time are obtained from pressure sensors 4 aand 4 b. FIG.10 describes a blood vessel without stenosis. FIG. 13 describes a bloodvessel with a downstream stenosis. PWV may be either calculated usingProcedure 3 or known from prior art.

Data Analysis—In-Vitro Experimental Results

Reference is now made to FIG. 12 and 14. FIG. 12 describes pressurechanges versus time (number of samples), sampled at 5000 samples/sec.Data were obtained on the in vitro system described in FIGS. 5-7. Thesystem does not include stenosis inside the vessel, however farreflections occur from the system bath 44 right edge. FIG. 12 serves asa reference data for cases where stenosis does exist in a blood vessel.The vertical axis indicates the pressure values in units of mmHg. Thehorizontal axis indicated the number of samples. The two curves in FIG.12 indicate the pressure value at two different points along the vessel,at the location of the two pressure sensors 24 a and 24 b. The dashedline is used for pressure measured by the sensor 24A and dotted line forthe pressure measured by the sensor 24B.

FIG. 14 describes the pressure changes versus time as explained for FIG.12. Data acquisition was preformed using the system described in FIGS.4-6, with the presence of a stenosis, as described in FIG. 13. Thepressure pulse is similar to the pulse generated for the case describedin FIG. 12 (without stenosis). When a stenosis exist in a blood vessel,a visible and detectable change in the pattern of the pressure waves canbe identified. This change is caused by the reflection of the pressurewave from the occluded site. The use of two transducers allows accurateidentification of the reflection point. The pressure wave created by thepressure generator 5 advances and reaches first the upstream pressuresensor 24A and later the downstream sensor 24B, so that a time delay,Dt, exist between the signal measured by the pressure sensor 24 a andthe signal measured by the pressure signal 24 b. The pressure wavemeasured by the upstream sensor (24 a) is ahead of the pressure measuredby the downstream sensor (24 b). In FIG. 13, the dashed line is used forpressure measured by sensor 24A and dotted line for sensor 24B.

When a stenosis exist the reflected wave reaches first the downstreamsensor 24B and later the upstream sensor 24A. This causes a change inthe order of propagation of the two waves, so that the pressure wavemeasured by the downstream sensor 24 b is now ahead of the otherpressure wave 24 a. The change in the order of the propagating waves isan indication for the existence of reflection caused by a stenosis. Thepoint along the time axis, where the change in order of the propagatingwaves occurs, was used to determine the location of the stenosis.

Reference is now made to FIG. 15 and 16. The vertical axis representsthe pressure time derivative (dp/dt) as calculated from the data of FIG.12 and 14. The use of pressure time derivative instead of the pressuremay simplify the identification of the reflection point. FIG. 15presents the pressure time derivative versus time as measured by sensors24 a and 24 b in the case where the system does not include stenosis.FIG. 16 presents the pressure time derivative versus time obtained fromthe system with stenosis.

Output Results

1. Location of stenosis, aneurysm or vascular bed.

2. Pressure wave velocity.

METHOD NO.6: Two-Pressure Sensors—Analytical Method

Reference is now made to FIG. 11. Two pressure sensors 4 a and 4 b areinserted into the blood vessel 30 of interest via a standard connector 8connected to a catheter 3. In another embodiment, the pressure sensors 4a and 4 b may be mounted on a mutual wire or catheter (e.g. Millar 2.5Fdual sensor model SPC-721, Millar Instruments Inc., Texas, U.S.A.). Inanother embodiment, the pressure sensor 4 a may be a fluid filledmanometer sensor connected to the catheter 3 via the connector 8. Thepulse generator 5 applies a pressure pulse. Data of pressure versus timeare obtained from pressure sensors 4 a and 4 b.

Data Analysis

The system uses the dual pressure function procedure (Procedure 1)described above, to detect the existence and location of stenosis,aneurysm or vascular bed. The system uses the method described in FIG.17 to estimate the severity of stenosis or aneurysm.

Output Results

1. Location of stenosis, aneurysm or vascular bed.

2. Stenosis or aneurysm severity.

3. Pressure wave velocity.

In-Vitro Experimental Results

FIG. 19 illustrates the application of the procedure on two pressurein-vitro data, where one pressure transducer was 12 cm and a secondpressure transducer was located 7 cm upstream the stenosis. FIG. 19apresents the pressure versus time as measured by the upstream sensor,Pa(t), located at A, 12 cm from the stenosis. FIG. 19b presents thepressure as measured by the downstream sensor, Pb(t), located at B, 7 cmfrom the stenosis. The result of the Procedure 1 is presented in FIG.19c, where the 2 peaks, of the input pressure wave (PI), and thereflected wave (PR) can be clearly observed. The time interval betweenthe two peaks is calculated from the graph—10 msec. Knowing the velocityof the pressure wave, 14 m/sec, allows calculating the stenosislocation: 0.01×14/2=0.07 m, which is a perfect match to the experimentsetup. Stenosis severity or reflection coefficient was calculatedaccording to the area ratio, as explained above. The calculatedcoefficient is 0.317. A third pressure sensor was located 2 cm fromstenosis. The same procedure was applied again and results are presentedin FIG. 19d. Calculated distance using the time difference between thepeaks (3 msec) is 2.1 cm, and the reflection coefficient is 0.316. Thesame reflection coefficient was expected and calculated for bothtransducers at 2 cm and 7 cm, in reference to the same stenosis.Verification for the value of the expected reflection coefficient isoffered by the equation R_(f)=(Ao−As)/(Ao+As) presented hereinabove:Ao=16 mm², As=9 mm² then R_(F)=7/25=0.28. Moreover, applying theProcedure 2 on the same data resulted in a reflection coefficient of0.34, and the same calculated distance, as presented in FIG. 19e.

METHOD NO.7: Flow Rate Measurement

Data Acquisition

The system used for data acquisition is described in FIG. 9. A flow ratesensor (replacing the pressure transducer 4) is inserted into the bloodvessel of interest 30 and positioned at point A. Pressure pulse isapplied by the pulse generator 5 and data of flow rate versus time Qa(t)at point A, are obtained.

Data Analysis

Reference is now made to FIG. 21-22, presenting data acquired on thein-vitro system described in FIGS. 4-7 and modified to include anultrasonic flowmeter (model T206, Transonic Systems Inc., New York,U.S.A.) and a stenosis 55, as shown in FIG. 20. FIGS. 21 and 22 presentthe flow rate changes versus time (number of samples). A sharp increasein the flow rate when pressure excitation is applied by the pulsegenerator 5, followed by a gradual decay. This response is similar tothe pressure signal. Therefore, all methods of analysis described forthe pressure signals are applicable. Visual inspection of FIGS. 21,reveals a change in the signal development marked P2, corresponding tothe reflection from a stenosis at 95 cm distance. Using the observedtime delay of 683 samples (equivalent to 136.6 msec), we get0.1366×13.9/2=95 cm. FIG. 22, reveals a change in the signal developmentmarked P2, corresponding to the reflection from a stenosis at 50 cmdistance. Using the observed time delay of 74.6 msec, we get0.0746×13.9/2=52 cm. These calculations are based on a pressure wavevelocity, 13.9 m/sec, deduced from pressure data acquired with twopressure transducers located 5.5 cm apart, using Procedure 3, and shownin FIG. 23.

The change in the signal, designated P2, presented in FIGS. 21 and 22differs from the change in the pressure signals observed above. Thedifferent reflection appearance originates from the fact that a forwardflow is reflected as a refraction wave, as a negative flow, thereforethe superposition of the forward and backward flows result in a decreasein amplitude (‘a valley’) and not an increase as observed with thepressure signals.

In all the in-vitro examples given above, the PSG module was built usingthe presented technique of a gun pistol (FIG. 8). However, as describedhereinabove, other embodiment includes the Bio-Tek, blood pressuresystems calibrator Model 601A, Vermont, U.S.A. FIG. 24 presents dataacquired on the in-vitro system described in FIGS. 4-7 with two pressuretransducers 24 a and 24 b, with a pressure excitation pulse generated bythe Bio-Tek calibrator, as a step function. FIG. 24 shows the stepsignal and the reflection from a stenosis 85 cm away. Using the derivedtime delay 114.2 msec, and a pressure wave velocity of 15 m/sec, theright distance is calculated. A PSG of this type is illustrated by FIGS.29, 30 and 31 in which a pump with an electromagnetic push/pullmechanism is used to control the rapid flow of fluid needed to generatea desired pressure pulse and an external electronic pulse generator isused for excitation.

Alternatively, FIG. 32 illustrates a PSG device having an externalelectromagnetic hammer giving a punch to a full-of-fluid membrane. Theresulting punch causes a pressure pulse signal to be generated. AnotherPSG device is illustrated by FIG. 33 in which two separate membranechambers having fluid volumes. One of the chambers is high pressurerelative to the other. An external electromagnetic hammer moves ordestroys a membrane separating the two chambers thereby generating thepressure signal. Finally, FIG. 34 illustrates a PSG device having a twoay linearly proportional flow control valve operated by straight DCdrive signals. The valve when opened releases high pressure fluid thatresults in the generation of a pressure signal. As can be seen fromthese embodiments, many different variations on flow and pressure may beutilized either alone or in combination to generate the pressure signal.

It will be understood that certain features and sub-combinations are ofutility and may be employed without reference to other features andsub-combinations as they are outlined within the claims. While thepreferred embodiment and application of the invention has beendescribed, it is apparent to those skilled in the art that the objectsand features of the present invention are only limited as set forth inclaims attached hereto.

What is claimed is:
 1. An apparatus for detecting, locating andcharacterizing changes in a tubular conduit system within a living bodyfor transferring fluids, said apparatus comprising: a signal generatorconfigured to transmit into said tubular conduit a probe signal thatchanges in response to encountering changes in said tubular conduitsystem; a signal sensor operative to receive said probe signal followingtransmission into said tubular conduit system; a processor unitoperatively connected to said signal sensor; a program for controllingthe processor unit; said processor unit operative with said program toreceive said probe signal following transmission through said tubularconduit system: identify changes in said probe signal; detectcharacteristics of said tubular conduit system, said characteristics ofsaid tubular conduit system being derived from changes in said probesignal; and recognize and assign a value of said characteristic of saidtubular conduit system.
 2. The apparatus according to claim 1, whereinsaid processor unit is operative to select a method from a plurality ofmethods to identify changes in said probe signal and therefrom detectchanges in said tubular conduit system.
 3. The apparatus according toclaim 1, wherein said tubular conduit system is a blood vessel systemand said processor unit is operative to detect changes in arterialcharacteristics.
 4. The apparatus according to claim 3 wherein saidprocessor unit is operative to detect aneurysms.
 5. The apparatusaccording to claim 3 wherein said processor unit is operative to detectstenosis.
 6. The apparatus according to claim 3 wherein said processorunit is operative to detect arterial occlusions.
 7. The apparatusaccording to claim 1 wherein said signal generator is a pressure signalgenerator.
 8. The apparatus according to claim 1 wherein said signalgenerator is a flow signal generator.
 9. The apparatus according toclaim 7 wherein said signal sensor is a pressure sensor.
 10. Theapparatus according to claim 8 wherein said signal sensor is a pressuresensor.
 11. The apparatus according to claim 7 wherein said signalsensor is a flow sensor.
 12. The apparatus according to claim 7 whereinsaid signal sensor is adapted to measure change in a cross-sectionaldiameter of said tubular conduit.
 13. The apparatus according to claim 7wherein said signal sensor is an intravascular flow sensor.
 14. Theapparatus according to claim 7 wherein said signal sensor is an externalimaging device.
 15. The apparatus according to claim 3 wherein saidarterial characteristics are selected from the group consisting ofaneurysms, stenosis, occlusion, dissection and stent multipositioning.16. The apparatus according to claim 8 wherein said signal sensor is aflow sensor.
 17. The apparatus according to claim 8 wherein said signalsensor is adapted to measure change in a cross-sectional diameter ofsaid tubular conduit.
 18. The apparatus according to claim 8 whereinsaid signal sensor is an intravascular flow sensor.
 19. The apparatusaccording to claim 8 wherein said signal sensor is an external imagingdevice.
 20. The apparatus according to claim 3 wherein said signalgenerator is a pressure signal generator; said signal sensor is apressure signal sensor; and said processor unit is operative to receivea heart beat signal; and synchronize receipt of said probe signal withsaid heart beat signal.
 21. The apparatus according to claim 3 whereinsaid probe signal is a plurality of discrete signals; said processorunit is operative to sample said discrete signals and receive andcalculate pressure wave velocity data.
 22. The apparatus according toclaim 21 wherein said processor unit is operative to perform a singlepressure function using said discrete signals and said pressure wavevelocity data.
 23. The apparatus according to claim 21 wherein saidprocessor unit is adapted to characterize the distensibility and thecompliance of lesioned and non-lesioned parts of blood vessels.
 24. Theapparatus of claim 22 wherein said processor unit when performing saidsingle pressure function is operative to calculate an allpass value anda cepstrum value from said minimum phase component; separate a regularpart and a singular part of said cepstrum value, where said singularpart and said regular part form said pressure wave; calculate anexponential function of singular part; evaluate a second peak time delaywith respect to a forward found in said pressure signal; evaluate acoefficient by calculation of a second peak amplitude to determine anarterial characteristic; and evaluate a location and severity of saidarterial characteristic.
 25. The apparatus of claim 3 wherein saidsignal sensor includes two sensing transducers disposed in spaced apartrelation.
 26. The apparatus of claim 25 wherein said processor unit isoperative to receive a forward pressure wave signal from a firsttransducer and a probe signal represented by a plurality of discretesignals sampled overtime.
 27. The apparatus according to claim 26wherein said processor unit is operative to perform a dual pressurefunction.
 28. The apparatus of claim 27 wherein said processor unit whenperforming said dual pressure function is operative to: calculate anallpass component and cepstrum component of a minimum phase component ofsaid forward pressure wave signal received from said signal sensor;apply an inverse filtering of said forward pressure wave signal; applysmoothing by a B-spline function; detect a forward peak location by aglobal maximum calculation; receive a threshold value; detect a secondpeak location by comparison with said threshold, where said threshold isderived from a forward peak maximum value and minimum size of acharacteristic; evaluate a second peak time delay with respect to saidforward peak; evaluate a reflection coefficient by calculating a forwardand reflected peak area; and evaluate a location and severity of saidcharacteristic.
 29. The apparatus according to claim 25 wherein saidprocessor unit is operative to calculate a pressure wave velocity from apressure wave sensed by said first and second transducers.
 30. Theapparatus according to claim 3 wherein said signal sensor is movablebetween at least two positions relative to said tubular conduit systemand said processor unit is operative to calculate a pressure wavevelocity from signals received from said two positions.
 31. Theapparatus according to claim 1 wherein said processor unit includes ananalog to digital convertor.
 32. The apparatus according to claim 1wherein said signal sensor includes a signal conditioner.
 33. Theapparatus according to claim 1, wherein said tubular conduit system is aurinary vessel system and said processor unit is operative to detectchanges in urinary tract characteristics.
 34. The apparatus according toclaim 1, wherein said processor unit is further operative to ascertainand assign a value corresponding to the location and size of saidcharacteristic of said tubular conduit.
 35. The apparatus according toclaim 1, wherein said value is representative of a location of saidcharacterized changes.
 36. The apparatus according to claim 1, whereinsaid value is representative of a size of said characterized changes.37. A method for using a computer to detect, locate and characterizechanges in a tubular conduit system within a living body fortransferring fluids wherein said computer is operatively connected to asignal generator configured to transmit into said tubular conduit aprobe signal that changes in response to encountering changes in saidtubular conduit system and a signal sensor operative to receive saidprobe signal following transmission into said tubular conduit system,said method comprising the steps of: receiving said probe signalfollowing transmission through said tubular conduit system: identifyingchanges in said probe signal; detecting characteristics of said tubularconduit system, said characteristics of said tubular conduit systembeing derived from changes in said probe signal; and recognizing andassigning a value of said characteristic of said tubular conduit saidsystem.
 38. The method according to claim 37 including the steps ofascertaining and assigning a value corresponding to the location andsize of said characteristic of said tubular conduit.
 39. The methodaccording to claim 37 further including selecting a process from aplurality of processes identifying changes in said probe signal andtherefrom detecting changes in said tubular conduit system.
 40. Themethod according to claim 37, wherein said tubular conduit system is ablood vessel system, said method further including detecting changes inarterial characteristics.
 41. The method according to claim 40 includingdetecting aneurysms.
 42. The method according to claim 40 includingdetecting stenosis.
 43. The method according to claim 40 includingdetecting arterial occlusions.
 44. The method according to claim 40wherein said signal generator is a pressure signal generator, and saidsignal sensor is a pressure signal sensor; said method includingreceiving a heart beat signal; and synchronizing receipt of said probesignal with said heart beat signal.
 45. The method according to claim 40wherein said probe signal is a plurality of discrete signals; saidmethod including sampling said discrete signals and receiving pressurewave velocity data.
 46. The method according to claim 45 including thesteps of performing a single pressure function using said discretesignals and said pressure wave velocity data.
 47. The method of claim 46wherein said performing step includes the step of calculating an allpassvalue and a cepstrum value from said minimum phase component.
 48. Themethod of claim 46 wherein said performing step includes the step ofseparating a regular part and a singular part of said cepstrum value,where said singular part and said regular part form said pressure wave.49. The method of claim 46 wherein said performing step includes thestep of calculating an exponential function of singular part.
 50. Themethod of claim 46 wherein said performing step includes the step ofevaluating a second peak time delay with respect to a forward found insaid pressure signal.
 51. The method of claim 46 wherein said performingstep includes the step of evaluating a coefficient by calculation of asecond peak amplitude to determine an arterial characteristic.
 52. Themethod of claim 46 wherein said performing step includes the step ofevaluating a location of said arterial characteristic.
 53. The method ofclaim 40 wherein said signal sensor includes two sensing transducersdisposed in spaced apart relation, said method includes the step ofreceiving a forward pressure wave signal from a first transducer and aprobe signal represented by a plurality of discrete signals sampledovertime.
 54. The method according to claim 53 further including thestep of calculating a pressure wave velocity from a pressure wave sensedby said first and second transducers.
 55. The method according to claim54 further including the step of performing a dual pressure function.56. The method of claim 55 wherein said performing step includes thestep of calculating an allpass component and cepstrum component of aminimum phase component of said forward pressure wave signal receivedfrom said signal sensor.
 57. The method of claim 46 wherein saidperforming step includes the step of applying an inverse filtering ofsaid forward pressure wave signal.
 58. The method of claim 56 whereinsaid performing step includes the step of applying smoothing by aB-spline function.
 59. The method of claim 56 wherein said performingstep includes the step of detecting a forward peak location by a globalmaximum calculation.
 60. The method of claim 56 wherein said performingstep includes the step of receiving a threshold value.
 61. The method ofclaim 56 wherein said performing step includes the step of detecting asecond peak location by comparison with said threshold, where saidthreshold is derived from a forward peak maximum value and minimum sizeof a characteristic.
 62. The method of claim 56 wherein said performingstep includes the step of evaluating a second peak time delay withrespect to said forward peak.
 63. The method of claim 56 wherein saidperforming step includes the step of evaluating a reflection coefficientby calculating a forward and reflected peak area.
 64. The method ofclaim 56 wherein said performing step includes the step of evaluating alocation of said characteristic.
 65. The method of claim 56 wherein saidperforming step includes the step of calculating a pressure wavevelocity from a pressure wave sensed by said first and secondtransducers.
 66. The method according to claim 39 wherein said signalsensor is movable between at least two positions relative to saidtubular conduit system, said method including the step of calculating apressure wave velocity from signals received from said two positions.67. The method according to claim 40 wherein said signal sensor is aflow sensor.
 68. The method according to claim 40 wherein said signalsensor is adapted to measure change in a cross-sectional diameter ofsaid tubular conduit.
 69. The method according to claim 40 wherein saidsignal sensor is an intravascular flow sensor.
 70. The method accordingto claim 40 wherein said signal sensor is an external imaging device.71. The method according to claim 40 wherein said arterialcharacteristics are selected from the group consisting of aneurysms,stenosis, occlusion, dissection and stent multipositioning.